Systems and methods for developing diagnostic tests based on biomarker information from legacy clinical sample sets

Abstract

Disclosed are systems and methods for developing diagnostic tests (e.g., detection, screening, monitoring, and prognostic tests) based on biomarker information from legacy clinical sample sets, for which only small sample volumes (e.g., about 0.05 to about 1.0 mL or less per sample) are typically available. For example, biomarkers (e.g., about 10, 50, 100, 150, 200, 300, or more) may be detected in the clinical samples through the use of single molecule detection and each biomarker may be detected in an assay that includes about 1 μL or less of a legacy clinical sample.

1. In a method of evaluating the health state of a live subject, comprising obtaining a measurement of at least one clinical biomarker from at least one live clinical sample isolated from said live subject, and inputting said measurement(s) into a model that calculates an output value correlated to said health state, the improvement comprising using as said model an algorithm that was developed by measurement of multiple development biomarkers comprising said clinical biomarker(s) from at least one legacy clinical sample set annotated for said health state, said measurement comprising use of legacy clinical samples having a sample volume of 1 ml or less, and analyzing said measurement of multiple biomarkers for an association with said health state. 
     
     
       2. The method of  claim 1 , wherein said measurement of multiple development biomarkers comprises measuring at least two biomarkers from said sample volume. 
     
     
       3. The method of  claim 2 , wherein said measurement of multiple development biomarkers comprises measuring at least 10 biomarkers from a sample volume less than about 0.5 milliliters. 
     
     
       4. The method of  claim 2 , wherein said measurement of multiple development biomarkers comprises measuring at least 20 biomarkers from said sample volume. 
     
     
       5. The method of  claim 2 , wherein said measurement of multiple development biomarkers comprises measuring at least 100 biomarkers from said sample volume. 
     
     
       6. The method of  claim 2 , wherein said measurement of multiple development biomarkers comprises measuring at least 200 biomarkers from said sample volume. 
     
     
       7. The method of  claim 2 , wherein said measurement of multiple development biomarkers comprises measuring at least 300 biomarkers from said sample volume. 
     
     
       8. The method of  claim 1 , wherein said measurement of multiple development biomarkers comprises, for each biomarker, measuring said biomarker in an assay of said legacy clinical sample, wherein said assay used about 1 microliter (uL) or less of said sample volume for each biomarker. 
     
     
       9. The method of  claim 8 , wherein at least 10 development biomarkers are measured per legacy clinical sample. 
     
     
       10. The method of  claim 8 , wherein said measurement of multiple development biomarkers used single molecule detection to measure said multiple development biomarkers in said legacy clinical sample. 
     
     
       11. The method of  claim 1 , wherein said health state is the presence or absence of a disease. 
     
     
       12. The method of  claim 1 , wherein said health state is pre-disease or a pre-disease condition. 
     
     
       13. The method of  claim 1 , wherein said health state is the risk of developing a disease. 
     
     
       14. The method of  claim 11 , wherein said absence of a health state is further defined to be a normal state or pre-disease state. 
     
     
       15. The method of  claim 1 , wherein said biomarkers comprise traditional laboratory risk factors.